title: Blocking von Willebrand factor for treatment of cutaneous inflammation.
abstract: Von Willebrand factor (VWF), a key player in hemostasis, is increasingly recognized as a proinflammatory protein. Here, we found a massive accumulation of VWF in skin biopsies of patients suffering from immune complex (IC)-mediated vasculitis (ICV). To clarify the impact of VWF on cutaneous inflammation, we induced experimental ICV either in mice treated with VWF-blocking antibodies or in VWF(-/-) mice. Interference with VWF led to a significant inhibition of the cutaneous inflammatory response. We confirmed the major findings in irritative contact dermatitis, a second model of cutaneous inflammation. In vivo imaging of cutaneous inflammation in the dorsal skinfold chamber revealed unaffected leukocyte rolling on anti-VWF treatment. However, we identified that reduced leukocyte recruitment is accompanied by reduced vascular permeability. Although VWF-mediated neutrophil recruitment to the peritoneum was described to require the VWF receptor on platelets (glycoprotein Ibα (GPIbα)), the VWF/GPIbα axis was dispensable for cutaneous inflammation. As assessed in tail bleeding assays, we could exclude interference of VWF blockade with hemostasis. Of particular importance, anti-VWF treatment was effective both in prophylactic and therapeutic administration. Thus, VWF represents a promising target for the treatment of cutaneous inflammation, e.g., leukocytoclastic vasculitis.
authors.affiliation: Department of Dermatology, University Hospital of Münster, Münster, Germany; Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany.
authors.forename: Carina
authors.initials: C
authors.lastname: Hillgruber
authors.affiliation: Department of Dermatology, University Hospital of Münster, Münster, Germany.
authors.forename: Annika K
authors.initials: AK
authors.lastname: Steingräber
authors.affiliation: Department of Dermatology, University Hospital of Münster, Münster, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Pöppelmann
authors.affiliation: Inserm U770, Université Paris Sud, Paris, France.
authors.forename: Cécile V
authors.initials: CV
authors.lastname: Denis
authors.affiliation: Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Ware
authors.affiliation: Department of Vascular Cell Biology, Max Planck Institute of Molecular Biomedicine, Münster, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.affiliation: Rudolf Virchow Center, University of Würzburg, Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: Department of Dermatology, Medical Faculty of Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Stefan W
authors.initials: SW
authors.lastname: Schneider
authors.affiliation: Department of Dermatology, University Hospital of Münster, Münster, Germany; Interdisciplinary Center for Clinical Research (IZKF), University of Münster, Münster, Germany. Electronic address: tobias.goerge@ukmuenster.de.
authors.forename: Tobias
authors.initials: T
authors.lastname: Goerge
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D007105:Immune Complex Diseases / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000276:immunology; D018366:Vasculitis, Leukocytoclastic, Cutaneous / Q000188:drug therapy* / Q000276:immunology; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*
chemical_list: D019138:Antibodies, Blocking; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor